109 results match your criteria: "The New York Stem Cell Foundation Research Institute[Affiliation]"
Nat Neurosci
December 2024
Pamela Sklar Division of Psychiatric Genomics, Department of Psychiatry or Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Stem Cells Transl Med
December 2024
The New York Stem Cell Foundation Research Institute, New York, NY 10019, United States.
Research conducted on the International Space Station (ISS) in low-Earth orbit (LEO) has shown the effects of microgravity on multiple organs. To investigate the effects of microgravity on the central nervous system, we developed a unique organoid strategy for modeling specific regions of the brain that are affected by neurodegenerative diseases. We generated 3-dimensional human neural organoids from induced pluripotent stem cells (iPSCs) derived from individuals affected by primary progressive multiple sclerosis (PPMS) or Parkinson's disease (PD) and non-symptomatic controls, by differentiating them toward cortical and dopaminergic fates, respectively, and combined them with isogenic microglia.
View Article and Find Full Text PDFCell Stem Cell
November 2024
Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK. Electronic address:
Senescent neural progenitor cells have been identified in brain lesions of people with progressive multiple sclerosis (PMS). However, their role in disease pathobiology and contribution to the lesion environment remains unclear. By establishing directly induced neural stem/progenitor cell (iNSC) lines from PMS patient fibroblasts, we studied their senescent phenotype in vitro.
View Article and Find Full Text PDFbioRxiv
September 2024
Roseman University, South Jordan, Utah, United States of America.
Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene, encodes the enzyme NAA10, as the catalytic subunit for the N-terminal acetyltransferase A (NatA) complex, including the accessory protein, NAA15. The first human disease directly involving was discovered in 2011, and it was named Ogden syndrome (OS), after the location of the first affected family residing in Ogden, Utah, USA.
View Article and Find Full Text PDFCell Stem Cell
November 2024
The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA. Electronic address:
Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS), resulting in neurological disability that worsens over time. While progress has been made in defining the immune system's role in MS pathophysiology, the contribution of intrinsic CNS cell dysfunction remains unclear. Here, we generated a collection of induced pluripotent stem cell (iPSC) lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures.
View Article and Find Full Text PDFThe emergence of brain organoids has revolutionized our understanding of neurodevelopment and neurological diseases by providing an in vitro model system that recapitulates key aspects of human brain development. However, conventional organoid protocols often overlook the role of microglia, the resident immune cells of the central nervous system. Microglia dysfunction is implicated in various neurological disorders, highlighting the need for their inclusion in organoid models.
View Article and Find Full Text PDFNutrients
June 2024
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC.
View Article and Find Full Text PDFRecent findings from studies involving astronauts and animal models indicate that microgravity increases immune cell activity and potentially alters the white and gray matter of the central nervous system (CNS). To further investigate the impact of microgravity on CNS cells, we established cultures of three-dimensional neural organoids containing isogenic microglia, the brain's resident immune cells, and sent them onboard the International Space Station. When using induced pluripotent stem cell (iPSC) lines from individuals affected by neuroinflammatory and neurodegenerative diseases such as multiple sclerosis (MS) and Parkinson's disease (PD), these cultures can provide novel insights into pathogenic pathways that may be exacerbated by microgravity.
View Article and Find Full Text PDFStem Cell Reports
February 2024
Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA; Department of Surgery, University of Arizona College of Medicine, Tucson, AZ 85724, USA; BIO5 Institute, University of Arizona, Tucson, AZ 85724, USA. Electronic address:
Successful allogeneic human pluripotent stem cell (hPSC)-derived therapies must overcome immunological rejection by the recipient. To build reagents to define these barriers, we genetically ablated β2M, TAP1, CIITA, CD74, MICA, and MICB to limit expression of HLA-I, HLA-II, and natural killer (NK) cell activating ligands in hPSCs. Transplantation of these cells that also expressed covalent single chain trimers of Qa1 and H2-K to inhibit NK cells and CD55, Crry, and CD59 to inhibit complement deposition led to persistent teratomas in wild-type mice.
View Article and Find Full Text PDFStem Cell Reports
January 2024
Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY, USA. Electronic address:
While studied extensively in model systems, human gastrulation remains obscure. The scarcity of fetal biological material as well as ethical considerations limit our understanding of this process. In vitro attachment of natural blastocysts shed light on aspects of the second week of human development in the absence of the morphological manifestation of gastrulation.
View Article and Find Full Text PDFGlia
March 2024
Neuroscience Institute, NYU Grossman School of Medicine, New York, New York, USA.
Astrocytes are a heterogeneous population of central nervous system glial cells that respond to pathological insults and injury by undergoing a transformation called "reactivity." Reactive astrocytes exhibit distinct and context-dependent cellular, molecular, and functional state changes that can either support or disturb tissue homeostasis. We recently identified a reactive astrocyte sub-state defined by interferon-responsive genes like Igtp, Ifit3, Mx1, and others, called interferon-responsive reactive astrocytes (IRRAs).
View Article and Find Full Text PDFNat Neurosci
January 2024
Neuroscience Institute, NYU Grossman School of Medicine, New York City, NY, USA.
Lancet Diabetes Endocrinol
December 2023
Department of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UK. Electronic address:
Background: Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes.
View Article and Find Full Text PDFNat Neurosci
October 2023
Neuroscience Institute, NYU Grossman School of Medicine, New York City, NY, USA.
Macroglia (astrocytes and oligodendrocytes) are required for normal development and function of the central nervous system, yet many questions remain about their emergence during the development of the brain and spinal cord. Here we used single-cell/single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) to analyze over 298,000 cells and nuclei during macroglia differentiation from mouse embryonic and human-induced pluripotent stem cells. We computationally identify candidate genes involved in the fate specification of glia in both species and report heterogeneous expression of astrocyte surface markers across differentiating cells.
View Article and Find Full Text PDFSLAS Technol
June 2024
Department of Anatomy and Physiology, The University of Melbourne, VIC, Australia. Electronic address:
Age-Related Macular Degeneration (AMD) is a highly prevalent form of retinal disease amongst Western communities over 50 years of age. A hallmark of AMD pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium (RPE), a biological process also observable in vitro. The accumulation of drusen has been shown to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development.
View Article and Find Full Text PDFbioRxiv
August 2023
The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA.
Multiple sclerosis (MS) is considered an inflammatory and neurodegenerative disease of the central nervous system, typically resulting in significant neurological disability that worsens over time. While considerable progress has been made in defining the immune system's role in MS pathophysiology, the contribution of intrinsic CNS-cell dysfunction remains unclear. Here, we generated the largest reported collection of iPSC lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures.
View Article and Find Full Text PDFSLAS Discov
October 2023
The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA. Electronic address:
The increasing use of automation in cellular assays and cell culture presents significant opportunities to enhance the scale and throughput of imaging assays, but to do so, reliable data quality and consistency are critical. Realizing the full potential of automation will thus require the design of robust analysis pipelines that span the entire workflow in question. Here we present FocA, a deep learning tool that, in near real-time, identifies in-focus and out-of-focus images generated on a fully automated cell biology research platform, the NYSCF Global Stem Cell Array®.
View Article and Find Full Text PDFBiol Reprod
October 2023
Department of Surgery, Weill Cornell Medicine, New York, NY, USA.
Niche-derived growth factors support self-renewal of mouse spermatogonial stem and progenitor cells through ERK MAPK signaling and other pathways. At the same time, dysregulated growth factor-dependent signaling has been associated with loss of stem cell activity and aberrant differentiation. We hypothesized that growth factor signaling through the ERK MAPK pathway in spermatogonial stem cells is tightly regulated within a narrow range through distinct intracellular negative feedback regulators.
View Article and Find Full Text PDFiScience
July 2023
Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy.
View Article and Find Full Text PDFbioRxiv
June 2023
Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.
Allogeneic human pluripotent stem cell (hPSC)-derived cells and tissues for therapeutic transplantation must necessarily overcome immunological rejection by the recipient. To define these barriers and to create cells capable of evading rejection for preclinical testing in immunocompetent mouse models, we genetically ablated , , , , , and to limit expression of HLA-I, HLA-II, and natural killer cell activating ligands in hPSCs. Though these and even unedited hPSCs readily formed teratomas in cord blood-humanized immunodeficient mice, grafts were rapidly rejected by immunocompetent wild-type mice.
View Article and Find Full Text PDFNat Med
January 2023
Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Adv Healthc Mater
April 2023
Tandon School of Engineering, New York University, 6 Metrotech, Brooklyn, NY, 11201, USA.
Reproducing in vitro the complex multiscale physical features of human tissues creates novel biomedical opportunities and fundamental understanding of cell-environment interfaces and interactions. While stiffness has been recognized as a key driver of cell behavior, systematic studies on the role of stiffness have been limited to values in the KPa-MPa range, significantly below the stiffness of bone. Here, a platform enabling the tuning of the stiffness of a biocompatible polymeric interface up to values characteristic of human bone is reported, which are in the GPa range, by using extremely thin polymer films on glass and cross-linking the films using ultraviolet (UV) light irradiation.
View Article and Find Full Text PDFStem Cell Reports
December 2022
The New York Stem Cell Foundation Research Institute, New York, NY 10019, USA. Electronic address:
Cell Reprogram
December 2022
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
Nat Neurosci
November 2022
Pamela Sklar Division of Psychiatric Genomics, Department of Psychiatry or Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains.
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